82 replies to this topic

[Rags847]

This site (ImmInst) isn't only interested in short-term benefits (immediate enhancement), but it's obviously dedicated to long-term benefits (health, life extension, etc).
So what do you all think are (or would be) the long-term effects of chronic use of Modafinil?
And what seems to be the long-term effects of chronic use of ADHD drugs (Adderall, Ritalin, etc)?

I like the effects and the no/low side effects of Modafinil. It seems to work great for me.
But I'm thinking of trying to get an ADHD diagnosis and obtain the ADHD drugs to see their effect.
Yet, I have more of a concern regarding ADHD drugs and long-term use, than I do with Modafinil.
Any good research out there on this topic?

Edited by Rags847, 20 February 2008 - 07:25 AM.

[purerealm]

well if you just reverse the primary effects of some of these drugs, adhd drugs probably reduce your memory and concentration in the long run, for modafinil i'm not sure because it's not known to be neurotoxic but for the adhd amphetamine drugs i am quite sure that the significant toxicity can significantly damage those areas of cognition.

[medievil]

well if you just reverse the primary effects of some of these drugs, adhd drugs probably reduce your memory and concentration in the long run, for modafinil i'm not sure because it's not known to be neurotoxic but for the adhd amphetamine drugs i am quite sure that the significant toxicity can significantly damage those areas of cognition.

none of these drugs are proven toxic and there are manu succes stories in the long run on many add message boards, only tolerance seems to be an issue sometimes

[purerealm]

what does that even mean, that drugs are not proven to be toxic? you'd have to be missing a few chromosomes to seroiusly believe that amphetamines are non-toxic. in fact, they are very toxic, they permanent deplete dopamine in rhesus monkeys

on bbc there was just an article reporting on how adhd drugs are more often than not NOT effective in the long run.

[dr_chaos]

what does that even mean, that drugs are not proven to be toxic? you'd have to be missing a few chromosomes to seroiusly believe that amphetamines are non-toxic. in fact, they are very toxic, they permanent deplete dopamine in rhesus monkeys

strattera: no hints for neurotoxicity. but it's not amphetamine like.
methylphenidate: no hints for neurotxicity.
amphetamine: jury still out. we just don't know yet.

Update on amphetamine neurotoxicity and its relevance to the treatment of ADHD.

Advokat C.Louisiana State University, Baton Rouge, LA 70803, USA. cadvoka@lsu.edu

OBJECTIVE: A review of amphetamine treatment for attention-deficit/hyperactivity disorder (ADHD) was conducted, to obtain information on the long-term neurological consequences of this therapy. METHOD: Several databases were accessed for research articles on the effects of amphetamine in the brain of laboratory animals and ADHD diagnosed individuals. RESULTS: In early studies, high doses of amphetamine, comparable to amounts used by addicts, were shown to damage dopaminergic pathways. More recent studies, using therapeutic regimens, appear contradictory. One paradigm shows significant decreases in striatal dopamine and transporter density after oral administration of "therapeutic" doses in primates. Another shows morphological evidence of "trophic" dendritic growth in the brains of adult and juvenile rats given systemic injections mimicking "therapeutic" treatment. Imaging studies of ADHD-diagnosed individuals show an increase in striatal dopamine transporter availability that may be reduced by methylphenidate treatment. CONCLUSION: Clarification of the neurological consequences of chronic AMPH treatment for ADHD is needed.

[purerealm]

those are using therapeutic doses, those dosages are unsustainable in the long run for most people. I started out with 10 mg of amphetamine giving me a 5 hour windows of primary effects, when i last used I was taking 200 mg giving me 2 hours of effects followed by an entire day of feeling shitty.

[medievil]

what does that even mean, that drugs are not proven to be toxic? you'd have to be missing a few chromosomes to seroiusly believe that amphetamines are non-toxic. in fact, they are very toxic, they permanent deplete dopamine in rhesus monkeys

on bbc there was just an article reporting on how adhd drugs are more often than not NOT effective in the long run.

LOL, none of these drugs are proven toxic, not provezn to be non toxic too but i dont beleive they are

@purerealm
look into DXM
however it prevents a tolerance,i dont know how you can reverse one

[purerealm]

DXM is also neurotoxic.

[dr_chaos]

those are using therapeutic doses, those dosages are unsustainable in the long run for most people. I started out with 10 mg of amphetamine giving me a 5 hour windows of primary effects, when i last used I was taking 200 mg giving me 2 hours of effects followed by an entire day of feeling shitty.

Maybe you should not use them then? Furthermore 200mg?

[medievil]

DXM is also neurotoxic.

have you got any proof that it is neurotoxic in therapetic doses?

[graatch]

you'd have to be missing a few chromosomes to seroiusly believe that amphetamines are non-toxic. in fact, they are very toxic, they permanent deplete dopamine in rhesus monkeys

At massive doses

those are using therapeutic doses, those dosages are unsustainable in the long run for most people.

Prove that "for most people" the doses are unsustainable. Most people can take the same dose of psychostimulant for years or more -- unless they're chasing the transient euphoria.

One of the guys on addforums switches from a methylphenidate product to an amphetamine product (and vice versa) at the end of every year, and this has worked well for him for 15 years. In his midthirties he's finishing his degree and going to medical school.

I started out with 10 mg of amphetamine giving me a 5 hour windows of primary effects, when i last used I was taking 200 mg giving me 2 hours of effects followed by an entire day of feeling shitty.

So you were abusing it. Entirely different.

The euphoria develops tolerance much faster than the therapeutic effects, to which one can actually develop reverse tolerance (ie sensitization).

DXM is also neurotoxic.

Not proven to occur at humans in any dose.

Edited by graatch, 02 March 2008 - 11:52 AM.

[purerealm]

i thought that the reverse tolerance was to the negative effects of amphetamine, it takes less mg to develop insomnia and other side effects. i don't use amphetamine anymore.

[medievil]

you'd have to be missing a few chromosomes to seroiusly believe that amphetamines are non-toxic. in fact, they are very toxic, they permanent deplete dopamine in rhesus monkeys

At massive doses

those are using therapeutic doses, those dosages are unsustainable in the long run for most people.

Prove that "for most people" the doses are unsustainable. Most people can take the same dose of psychostimulant for years or more -- unless they're chasing the transient euphoria.

One of the guys on addforums switches from a methylphenidate product to an amphetamine product (and vice versa) at the end of every year, and this has worked well for him for 15 years. In his midthirties he's finishing his degree and going to medical school.

I started out with 10 mg of amphetamine giving me a 5 hour windows of primary effects, when i last used I was taking 200 mg giving me 2 hours of effects followed by an entire day of feeling shitty.

So you were abusing it. Entirely different.

The euphoria develops tolerance much faster than the therapeutic effects, to which one can actually develop reverse tolerance (ie sensitization).

DXM is also neurotoxic.

Not proven to occur at humans in any dose.

very good post!

[Yearningforyears]

Hypertension maybe?

[purerealm]

my blood pressure was ten to twenty points higher when i was on adderall, this happened with provigil as well.

another side effect is that the learning that you do while on adderall and ritalin stays with the drug, as in once you stop taking them the period that you were using is hard to recall, this is a worrisome side effect because it's another abuse factor.

[dr_chaos]

my blood pressure was ten to twenty points higher when i was on adderall, this happened with provigil as well.

high bp is a known side effect of stimulants, but since you were overdosing them that much... seriously it's your own fault. furthermore it's common to quit them if they don't stop giving you such effects after some days.

another side effect is that the learning that you do while on adderall and ritalin stays with the drug, as in once you stop taking them the period that you were using is hard to recall, this is a worrisome side effect because it's another abuse factor.

Source?

[purerealm]

i'm not saying that it happens to everybody but the state-dependent learning is common to a certain degree with every drug, and for me it is especially poignant with stimulants. It is common sense. If you are using stimulants to help w/ memory and concentration, it is only logical that when you are not on it, your memory and concentration are going to be even worse than before. The thing with the adderall is that it stopped losing its effectiveness after about 30 mg. After the 30 mg, I had to take 50 mg.
After that, I decided to wait a week to see if my tolerance would die down, it didn't.
I waited 4 more days but I had finals to study for so instead I opted to up the dosage, half-knowing that the dose would be unsustainable to carry me through all of my finals.

Before that my dosage was at around 20 mg, I waited the entire summer (2.5 months) and coming back my tolerance was a little better but nowhere near as good as before.

So to reiterate, the number of doses it took me to get from ~30 to ~200 mg was something like 4 doses. 4 DOSES.

Sure the stimulants might do you good, but why risk your mind and body? Wouldn't it be better to err in favor of your health? For some reason some of the members of this life-extension related forum don't seem to be concerned about harm reduction. But before you go decide to go the stimulant route go visit some ADD forums, there are many people out there who do not take adderall anymore, because they cannot take it anymore.

[Undaunted]

I also took Adderall for ADHD-Inattentive Type. Like mentioned, I found over time I had to start increasing the dosage (up to 80 mgs) to achieve the same prior effectiveness. I was about ready to forego Adderall altogether and search for a new treatment when I stumbled accross the clinical trial results for Provigil. To make a long story short, it was a miracle. I found I was able to take a small dose of Provigil (50 mg) 2x a day along with the Adderall for a pure lucidity I hadn't achieved before. An additional side benefit the Provigil (alertness drug) provided was, over a short period of time I was able to significantly reduce my Adderall dosage from 80 mgs per day down to 5 mgs - yes, you read that right 5 mgs! I think the reason for this is the Provigil provides alertness and allays fatigue while the Adderall is able to zero-in and deal with the focus (or lack thereof) aspect of our problem.

Here is the dosage schedule that works best for me: 9:00 AM take 50 mgs Provigil and 2.5 mgs Adderall with late breakfast or low-carb mid-morning snack . . . Immediately after lunch take 50 mgs Provigil and 2.5 mgs Adderall. The Provigil will also diminish the drop-off or let-down you experience when the adderall's effectiveness wears off. The great thing about Provigil versus other stimulants is once your body adapts to a dosage you can simply raise or lower your morning dosage (i.e. up or down 25 mgs) for just a couple days then you can return back to the normal dose again. It appears varying the dosage, either up or down, every fourth week for just a day or two will ensure you are achieving the maximum efficacy. Again you only need to vary the dosage for a day or so roughly once a month, then you return back to the original dosage. I have used this program for several years with great success.

[If you don't already, you should incorporate a light workout program at least 2-3 times a week and eat smaller balanced (30% protein, 45% carb, 25% unsaturated fat) meals throughout the day. You also should not eat simple carbohydrates, unless in combination with a little protein, as this will effect your blood sugar and sap your concentration and energy levels.]

I know just because this works for me doesn't necessarily mean it will for you. But if it works half as well for you as it has for me I guarantee you will be a very happy camper. Best wishes and please respond with your results.

Cheers!

[DrHealth]

Wow, sounds promising, if only adderal wasn't a restricted medication here in the UK :(

[mystery]

Undaunted, do you think modafnil is potentiating the adderall CNS effects? I'm hoping for this when I try it with d-amphetamine.

My concern with d-amphetamine is that I will build a tolerance, and become dependent on the effect, only to have it become ineffective. For this reason, I have restricted my d-amph use to 3-4 times a week, and only in a 2.5 mg dose. Even at this low dose, it still appears to be very helpful. It might even help improve focus on off days by inducing CNS changes that remain.

It's my opinion that ADHD stimulants may be beneficial long term on a low-dosing regieme, and taking holidays frequently. At least, this is going to be my strategy. And, if I build a tolerance under these conditions, than I won't be dependent on the effect and can easily just stop taking medication. I will investigate plenty of herbs and supplements to rotate with d-amph so I can take holidays frequently. My strategy is more or less that d-amphetamine (or focalin, desoxyn, or any other ADHD drug) will be an addition to my overall tratment plan, but not the one solution. I'm looking at it from a holistic point of view, and if d-amph helps marginally in a sustainable manner then I can certainly benefit from it, along with using other drugs, herbs, supplements, and lifestyle changes to cope.

[bgwithadd]

@mystery - this seems to be the best way to go. I have good results keeping my dose low and taking breaks.

@Isochroma - They've been using amphetamines since the 30s and it was in diet pills until the 70s. It's no secret high doses will cause big problems, but it's much less likely smaller doses will. The doses involved there are equivalent to about 80-100mg a day for a human. The recommended max dose is 60 mg for adderall, and most people take 20-30mg a day (I try to take just 10). It's also a lot of the reason I try hard to take lots of neuroprotectants. There's still cause for concern, though.

[Pike]

I actually have ADHD, and am prescribed with Adderall XR - 25mg and Adderall IR (generic) - 10mg. I won't lie: Adderall provides amazing treatment in more ways than I imagined. However, the stigma & generally anecdotal long-term side effects (which I found out LATER) of amphetamines are the ENTIRE reason I decided to start Nootropics.

After looking at the AMAZING anecdotes of Noots, and some first-hand experience, I took a long&hard think about my amphetamine treatment and weighed out the two situations:

1) I can go with amphetamines for the rest of my life to do a temporary quick-fix of my brain every single day, then end up with nerve damage when I hit 45 and gain the inability to hold a glass of coffee steadily in my hand without shaking.

2) I can go with nootropics and, essentially, come damned close to permanently correcting the chemical imbalance in my brain whilst simultaneously turning my brain into the Shelby GT500 of cognitive abilities; all from a laundry list of substances that come cheaper in 6 month quantities than my prescriptions (for 3 months) and are safer than tylenol.

It was an easy decision.

[bgwithadd]

I actually have ADHD, and am prescribed with Adderall XR - 25mg and Adderall IR (generic) - 10mg. I won't lie: Adderall provides amazing treatment in more ways than I imagined. However, the stigma & generally anecdotal long-term side effects (which I found out LATER) of amphetamines are the ENTIRE reason I decided to start Nootropics.

After looking at the AMAZING anecdotes of Noots, and some first-hand experience, I took a long&hard think about my amphetamine treatment and weighed out the two situations:

1) I can go with amphetamines for the rest of my life to do a temporary quick-fix of my brain every single day, then end up with nerve damage when I hit 45 and gain the inability to hold a glass of coffee steadily in my hand without shaking.

2) I can go with nootropics and, essentially, come damned close to permanently correcting the chemical imbalance in my brain whilst simultaneously turning my brain into the Shelby GT500 of cognitive abilities; all from a laundry list of substances that come cheaper in 6 month quantities than my prescriptions (for 3 months) and are safer than tylenol.

It was an easy decision.

Well, I have tried pretty much everything but I don't get to the level you describe, even taking about a dozen supplements every day. Much better, yes, but it's still not as good as taking adderall.

[purerealm]

I actually have ADHD, and am prescribed with Adderall XR - 25mg and Adderall IR (generic) - 10mg. I won't lie: Adderall provides amazing treatment in more ways than I imagined. However, the stigma & generally anecdotal long-term side effects (which I found out LATER) of amphetamines are the ENTIRE reason I decided to start Nootropics.

After looking at the AMAZING anecdotes of Noots, and some first-hand experience, I took a long&hard think about my amphetamine treatment and weighed out the two situations:

1) I can go with amphetamines for the rest of my life to do a temporary quick-fix of my brain every single day, then end up with nerve damage when I hit 45 and gain the inability to hold a glass of coffee steadily in my hand without shaking.

2) I can go with nootropics and, essentially, come damned close to permanently correcting the chemical imbalance in my brain whilst simultaneously turning my brain into the Shelby GT500 of cognitive abilities; all from a laundry list of substances that come cheaper in 6 month quantities than my prescriptions (for 3 months) and are safer than tylenol.

It was an easy decision.

what is your nootropic stack?

And Also, where did you read about shaky hands as a result of amphetamine use? I've got that too, can't hold my arm horizontally without a slight tremor.

[bgwithadd]

Is there any research on caffeine's neurotoxicity?

[Pike]

Well, I have tried pretty much everything but I don't get to the level you describe, even taking about a dozen supplements every day. Much better, yes, but it's still not as good as taking adderall.

Yeah, I'm pretty sure that there isn't a 100% sure-fire way to cure myself, but there's a certain permanently-long-term list of benefits I keep finding that closely resemble pretty much about everything I've been looking for in treating my ADHD (I only have a mild/moderate case of it), so to someone like me, these could provide a lot of benefit; perhaps even a second or third-rate "fix" if I respond well. However, you're quite right: Adderall is a fantastic treatment. Sometimes, though, I believe the toll it will be taking on my body will be directly proportional to the benefits that I currently get from it.

what is your nootropic stack?

And Also, where did you read about shaky hands as a result of amphetamine use? I've got that too, can't hold my arm horizontally without a slight tremor.

Hey, I didn't actually "read" about the shaky hands, but have been experiencing a bit of it first-hand. Also, I have some friends who have done quite a bit of amphetamines (not necessarily adderall... more like meth) and some of them have a hard time just holding a salt-shaker steady &whatnot. I've come to the conclusion that it essentially.... fucks up your nerves.

But that's besides the fact, there's a lot of literature out there that talks about the permanent nerve damage of amphetamines. I just never bothered to look for them, because it's pretty easy to see that the amphetamines are doing just that to me and everyone I know that uses them.

My stack is:
Piracetam
Centrophenoxine
L-Huperzine A (once in a while)
Sulbutamine

On Mondays through Fridays, I've found 3600mg to be quite fine 3 to 4 times daily. If I go with 3 times, I usually take 1800mg for the first dose w/breakfast and then just 900 twice more throughout the day. On weekends, I go with 5400mg spaced 3-4 times, going with 2700mg along w/breakfast, 1800mg at lunch, and the last 900 after dinner, or right before sleep (so I can have that lovely feeling of 900mg Piracetam flowing through me during sleep. I've found it's quite lovely to wake up too, as well.)

I use Centrophenoxine mainly as a choline source, however, I've also found that it's combination with Piracetam to be AMAZING. Then again, I've never actually just tried Piracetam without Centrophenoxine (after reading 948759845 threads with people complaining of splitting headaches due to choline shortage from the Piracetam working it overtime.) My current ratio is 1:4 for Cent (i.e. 800mg p/day w/3600mg Piracetam), however, I'm considering experimenting around with it, seeing as the common "nootropic dose" for Cent seems to be in the 1000-3000mg range. But regardless of whether or not Cent is an efficient choline source, its combo with Pi has been working splendidly for me.

I bought a bottle of L-Huperzine A a while ago, and just recently tried it. It may be that my body is just responding well to it, but... holy shit. That's all I have to say. That "elephant memory" that I read about... 100% true in my case w/Hup. I also managed to have a... very... vivid lucid dream the first time I tried it before going to sleep. On that note, to anyone to might be taking L-Hup, I truly *DO* reccomend splitting it up into 4 administrations throughout the day. Maybe not necessarily the maximum 400mcg that can be taken, but 4 admins in the day (w/the last one right before sleep) had a decidedly positive effect on me that was way better than 3 admins.

At the moment, I'm adding in a new Noot once every 2 or 3 weeks. I've *tried* Sulbutamine only once, and it's the next Noot to be added to my regimen. Just from trying it once, I know that this will be one I enjoy thoroughly. But if this godforsaken Idebenone will arrive in the mail before Thursday (the 2-week, new-noot markpoint) then I just might put that in front of Sul.

Check out my log on here if you want. I should be making an in-depth post concluding my first 2 weeks soon.

-Pike

[medicineman]

so far, the consensus points to:

-everything causes neuronal death.

i dont believe caffeine or ritalin or adderall, under certain doses cause long standing damage.

here are two studies that seem positive about ritalin.

http://www.ncbi.nlm....st_uids=9365033

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12604695

and the caffeine study. caffeine is generally poorly tolerated in neonate mammals via a couple of mechanisms. one, caffeine may interfere with iron absorption of the neonate, two, caffeine interferes with insulin activity in the neonate, and three, a neonate has no effective way of detoxifying itself of caffeine. I am assuming the neuronal death would be due to the same ol excitoxic mechanism, via calcium and other excitatory ions.

In high doses, even like water, it is toxic. On the other hand, here is a study showing that caffeine may be of aid in halting amyloid deposition in the brain.

http://www.nature.co...l/0705185a.html

there is also recent studies showing caffeine may have a role in parkinsons prevention.
i would be interested in reading about neuronal death due to caffeine intake in adult mammals.

Edited by medicineman, 06 January 2009 - 09:44 PM.

[bgwithadd]

In a sense, everything DOES cause neuronal death. Even neurotransmitters themselves do. The question is how severe and at what doses. Is it linear to dose or exponential?

Unfortunately they can't find real answers to this without cutting up the brains of people who do and don't use amphetamine at various doses and ages and measuring how many neurons they have, though some primate studies at lower (and perhaps higher) doses might give us some idea.

Also, all death is permanent, but new receptors should grow. I guess that's why neuroprotectants and neurogenesis are the most important thing I worry about lately. Things like lithium, piracetam, theanine and tuarine will hopefully keep the damage down a bit - and they do seem to help me somewhat from developing tolerance as I had hoped they would.